Diagnostic and prognostic relevance of plain radiographs for periprosthetic joint infections of the hip: a literature review

Conventional radiography is regularly used to evaluate complications after total hip arthroplasty. In various recent consensus meetings, however, plain radiographs of a potentially infected hip joint have been judged as being only relevant to exclude diagnoses other than infection. Solid data on radiographic presentations of periprosthetic joint infection (PJI) are scarce. As a result, the prognostic value of radiological features in low-grade PJI remains uncertain. The present review article aims to present an overview of the available literature and to develop ideas on future perspectives to define the diagnostic possibilities of radiography in PJIs of the hip. The primary outcome of interest of this systematic review was the radiologic presentation of periprosthetic joint infections of the hip. As secondary outcome of interest served the sensitivity and specificity of the radiologic presentation of periprosthetic joint infections. Of the included articles, 26 were reviews, essays, or case reports and only 18 were clinical studies. Typical radiologic abnormalities of PJI were a periosteal reaction, a wide band of radiolucency at the cement–bone or metal–bone interface, patchy osteolysis, implant loosening, bone resorption around the implant, and transcortical sinus tracts. The frequency of their occurrence is still inadequately defined. A deeper understanding of the underlying causes and the relation between microorganisms to radiologic abnormalities can probably help clinicians in the future to diagnose a PJI. This is why further research shall focus on the radiographic features of PJI.


Introduction
Conventional radiography is regularly used to evaluate joint prostheses after implantation and during followup, as X-rays can detect potential abnormalities involving both the implant and the surrounding bone.Such abnormalities could be for example periprosthetic fracture, dislocation, osteolysis due to third body wear, or sinking of the shaft.One of the major complications after arthroplasty is periprosthetic joint infection (PJI).In various recent consensus meetings, however, plain radiographs of a potentially infected hip joint have been judged as being only relevant to exclude diagnoses other than infection [1][2][3].In the consensus statement published by Romano and colleagues in 2020, for example, the diagnostic performance of conventional radiography in detecting PJI would be very low.
Furthermore, conventional radiography would show demineralization only when more than 30-50% of bone mass has been lost.Abnormalities of bone around the implant would usually be non-specific for infection.In addition, up to 50% of conventional X-ray exams would give negative results [1].In another recent consensus statement published by Signore et al. [2,3], the authors state that "Regarding PJI, conventional radiography often yields normal results or may detect non-specific signs of soft-tissue swelling.Serial plain radiography has been reported to have a sensitivity of 14% and specificity of 70% in detecting implant-associated infections [4].Radiographic signs that may reveal PJI with high specificity are gas formation and active, immature periostitis.Radiographic signs with low specificity include soft-tissue swelling, periprosthetic lucency, and component loosening.However, differentiation between septic and aseptic periprosthetic lucency and component loosening is almost impossible in conventional radiography.Also, these signs are visible only when almost 30% of the bone mass has been lost; thus, 50% of radiographs remain normal despite the presence of infection".These consensus statements are, however, only based on three references [5][6][7].
Most of the studies to which these statements relate date to the late 80 s and early 90 s [5,7,8].The foundations of the data referenced here are also quite weak, such as in the study from Tigges et al., [7] with 20 confirmed infected hip arthroplasties, or Lyons et al. [5] 50 painful hip arthroplasties.The largest series presented was from Thoren and Hallin in 1989 [8], where the authors analysed 102 hip revisions.Of these, however, only 47 were infected and the prostheses analysed were original Charnley prostheses which possessed a 22.225mm head in ultra-high molecular weight polyethylene (UHMW PE) in an all-cemented technique and a metalon PE bearing.The arthroplasty landscape has, however, largely changed since then.Today's arthroplasties often contain an uncemented cup and a ceramic head.Depending on the country the stem is often uncemented ranging from 37% in the National Joint Registry in Great Britain to 78% in the German Arthroplasty Registry in Germany [9].Uncemented stems usually consist of titanium which altogether changes the immunogenicity of the wear particles generated.Moreover, the annual number of patients treated with arthroplasties has multiplied and as such the surgical technique and postoperative rehabilitation protocols have been optimized and largely standardized.In addition, life expectancy has increased with people in old age having multiple comorbidities in addition to joint replacement.This supposedly changes the spectrum of bacteria responsible for infections.While we are quite effective in treating acute PJIs, the successful management of low-grade infections is still a challenge.This includes reliable, sensitive and specific diagnostics of such low-grade PJIs.Nevertheless, substantial progress has been made in the diagnosis of such an event with improvements in the histopathological analysis of the periprosthetic membrane [10,11], the advent of PCR analyses [12], and synovial fluid analysis including the analysis of PMNs, alpha-defensin or leukocyte esteraselevels [13][14][15][16].Other newer markers are presently under investigation, such as pentraxin-3 [17], calprotectin [18], or myeloperoxidase [19].Of note, thresholds for leukocytes in low-grade PJIs have been constantly lowered over the past decades ranging now-depending on the joint-between 1000 and 2000 leukocytes/µl only [20].Cultivation techniques for bacteria have also been more and more standardized.We can assume that the overall sensitivity and specificity have increased over the past 30 years.Similarly, the technique of acquiring radiographs has also improved with the widespread introduction of digital radiography.The digital data set allows for post-imaging optimization of each X-ray to visualize structures that were difficult to discern in traditional images intended for a good bone contrast only.Nevertheless, solid data on radiographic presentations of PJI are scarce.As a result, the prognostic value of radiological features in low-grade PJI remains uncertain.The present review article aims to present an overview of the available literature and to develop ideas on future perspectives to define the diagnostic possibilities of radiography in PJIs of the hip.

Eligibility criteria
All published articles related to the radiographic presentation of PJI of the hip were accessed.Only articles available in English, French, Spanish or German were eligible.
Original studies with a level of evidence of I to IV according to the Oxford Centre of Evidence-Based Medicine [21] plus review articles and essays were considered.

Selection and data collection
Three authors (UKH; MM; GE) independently performed the database search.All the resulting titles were screened and, if suitable, the abstract was accessed.The full text of the abstracts, which matched the topic, was accessed.A cross-reference of the bibliography of the full-text articles was also screened for inclusion.If the full text was not accessible or available, the article was not considered for inclusion.Disagreements were debated before final inclusion into the study.

Data items and outcome of interest
The following data at baseline were extracted: author, year of publication and journal, PMID/PCMID/DOI, type of analysis performed, country of origin, main study outline, number of patients used for the relevant statements, and statements made regarding radiography and PJI of the hip.A suitable level of evidence was attributed to each study.The primary outcome of interest was the radiologic presentation of PJI of the hip.As secondary outcome of interest served the sensitivity and specificity of the described image characteristics.

Study selection
The literature search resulted in 1248 articles (Fig. 1).After the removal of duplicates, 1121 articles were screened.Having screened titles and abstracts, the original manuscript was accessed for 71 studies.Of these 44 finally met the inclusion criteria, the other publications were either in Chinese (n = 3), not retrievable (n = 10), retracted (n = 1), were not related to the research question (n = 6), or did not directly report radiographic parameters (n = 7).Of the finally included articles, 26 were reviews, essays, or case reports.Only 18 publications were clinical studies with a level of evidence between IV and II.
Regarding risk factors for infection, an interesting observation was made by Rey Fernandez et al. who described that patients with more than 60 mm soft-tissue thickness over the greater trochanter had a sevenfold higher risk of infection [56].

Discussion
PJI is one of the most serious complications after total hip arthroplasty and poses major diagnostic challenges for clinicians.Radiological imaging, especially plain radiographs, is part of every diagnostic workup in case of suspected complications after total hip arthroplasty.There are plenty of reviews and original works dealing with the diagnostic algorithm of PJI.This review aimed to summarize and analyse the available information about the radiologic presentation of PJI and the frequency of appearance.Furthermore, we raised the question of whether the causative microorganisms differ regarding the radiologic presentation.
The first observation of this review is the lack of original data evaluating the radiologic characteristics of PJI of the hip.There are more reviews (n = 26) repeating findings of other studies than original works (n = 18).These reviews mainly concentrate on the diagnosis of PJI, however, they do not focus on the radiographic presentation of PJIs.As described in the section "results", the main statements regarding the radiologic presentation in the reviews are the above-mentioned radiologic pathologies.They do not report on the frequency of the radiologic findings and no correlation to causative microorganisms was analysed.Furthermore, the findings regarding the radiologic presentation of PJI of original works are often coproducts of other primary endpoints [5,44,46,48,50,51,53].
The next interesting finding of this review is the frequency of radiologic abnormalities in the case of a proven PJI of the hip.While some authors report radiographic changes in all of their PJI cases (100%) [44,45,47], other authors only presented abnormalities in 14-63% [48][49][50]57].Multiple reasons could explain this wide range.Therefore, having a closer look at the original works reporting the frequencies is necessary.The first possible explanation is the lack of a standardized followup to classify radiologic changes in the case of PJI.Some authors present radiographs already 6 months after surgery while other authors describe X-rays taken nine years postoperatively.The given collectives are mostly very small with numbers of patients between 6 and 20.Such collectives are not big enough to give sufficient information about the frequency of the appearance of radiological abnormalities.
Furthermore, the oldest and latest works reporting frequencies are separated by more than 40 years of medical evolution [45,47].The definition and the diagnostic algorithm have, however, relevantly changed since then and therefore these studies lack comparability [58,59].Similarly, the technique of acquiring radiographs has also improved with the advent of digital radiography.This allows post-imaging optimization of each X-ray to visualize also structures such as soft tissues that were difficult to discern in traditional images intended for a good bone contrast only.
When using radiographs not only to exclude differential diagnoses, but also to diagnose a PJI, sensitivity and specificity are crucial.Two original works are reporting about the diagnostic value with similar results.The sensitivity could be classified as low at 20-25% while the specificity of periosteal reactions and periarticular calcifications is moderate to good (79-92%) [5,52].Consequently, plain radiographs could be used to confirm PJI in the presence of characteristic radiologic abnormalities.Especially in the case of early PJI, the majority of cases of early PJI radiographs are still usually normal [43].As a consequence, the question of how to interpret and use radiographs to diagnose late PJIs and the diagnostic value of this technique remains equivocal with the analysed literature.
Having a look at radiographs taken after septic revisions of hip arthroplasties, three original works report heterotopic ossifications.Incidences range depending on the collective analysis between 12 and 84%.Brooker grades presented were mainly between one and three [53,54,60].Interestingly, when comparing aseptic and septic revisions, heterotopic ossifications are significantly more likely in septic cases (11 vs. 84%) and present with significantly higher Brooker grades [54].Consequently, some kind of interaction between soft tissue and the causing microorganisms can be assumed.This assumption is highlighted by the observation of Rey Fernández et al., that there is an association between higher soft-tissue thickness and risk for PJI after primary total hip replacements.Furthermore, patients with more than 60 mm soft-tissue thickness around the major trochanter had a sevenfold higher risk of PJI [56].Unfortunately, there are no data available considering the association between the causing microorganisms and soft-tissue changes.
Historically and as presented in the analysed reviews, characteristics that are described to recognize a PJI of the hip on a plain radiograph are periosteal reaction, a wide band of radiolucency at the cement-bone or metal-bone interface, patchy osteolysis, implant loosening, bone resorption around the implant, and transcortical sinus tracts.In cases of aseptic loosening, there is slow and progressive evolution, while in cases of infectious loosening, this loosening occurs rapidly, in a more aggressive manner and with greater bone destruction [7,61].Data regarding the frequency of occurrence of the named radiologic abnormalities in cases of PJI are insufficient.Prospective or at least retrospective analyses with larger collectives are necessary to evaluate the frequency and to define the diagnostic value of the radiologic presentation for the diagnosis of PJI.Furthermore, there is a lack of data analysing the association between the causative microorganisms and the radiologic appearance.Although imaging techniques like computer tomography [52,55,62] or magnetic resonance imaging [63] have been reported to also provide additional and helpful clues concerning the presence of a PJI such as periosteal reaction, capsule oedema, and intramuscular oedema, the mainstay in diagnosing PJI to date remains plain radiographs.

Conclusion
Typical radiologic abnormalities of PJI are periosteal reaction, a wide band of radiolucency at the cementbone or metal-bone interface, patchy osteolysis, implant loosening, bone resorption around the implant, and transcortical sinus tracts.The frequency of their occurrence is still inadequately defined.A deeper understanding of the underlying causes and the relation to microorganisms can probably help clinicians in the future to diagnose a PJI.This is why further research should still further evaluate the radiographic features and value in the context of PJI.

Fig. 1
Fig. 1 Flowchart of the literature search

Table 1
Review articles, essays, and case reports addressing the aspect of radiographic presentation of infected total hip arthroplasties

Table 2
Original studies addressing the aspect of radiographic presentation of infected total hip arthroplasties